LHRH is synthesized by the hypothalamus and released from neurons to travel through the portal system of the pituitary triggering the proestrous LH surge. Several factors determine the levels of the LHRH observed in the hypothalamus, the pituitary and the serum. There are the factors leading to the formation of LHRH (synthesis and secretion) and there are those factors leading to the destruction of LHRH. Reports document the existence in the hypothalamus, pituitary and blood of enzymatic activity fragmenting LHRH. In the act of altering the structure of LHRH, such activity decreases biological activity. Such enzyme activity may therefore represent a mechanism of partially controlling the levels of LHRH existing in the hypothalamus and pituitary and therefore play a determining role in the mammalian reproductive cycle. Preliminary data are presented indicating that the degradation of the synthetic substance leucine-p-nitroanilide is depressed in the hypothalamus and pituitary during the proestrous LH surge in coincidence with elevated levels of gonadal steroids. The degrading activity rises again shortly subsequent to proestrous in conjunction with falling steroid and LHRH levels. The indications are therefore that the degrading activity may be steroid modulated so as to be depressed during proestrous thereby allowing LHRH levels in the hypothalamus and pituitary to rise sufficiently at the site of biological action as to increase pituitary sensitivity and to trigger the preovulatory LH surge. Preliminary data have also shown that LHRH may be degraded by the same enzyme activity in that LHRH will inhibit degradation of the synthetic substrate. It may be therefore that the LHRH inactivating activity is steroid modulated in similar manner so as to be depressed in proestrous and contribute to the increased LHRH sensitivity of the proestrous pituitary. The present studies intended to investigate this possibility by determining (a) if the synthetic substrate and LHRH are degraded by a single enzyme, (b) if the degrading activity toward LHRH varys during the estrous cycle, (c) if the LHRH degrading activity is steroid modulable and (d) if so called "large" LHRH is capable of giving rise to biological activity as indicated by LH release from pituitary cell cultures.